[4] Growing up in New Haven, Pacelle enjoyed reading natural history and developed an early concern about the mistreatment of animals.

He attended Notre Dame High School and graduated with degrees in history and environmental studies from Yale University.

His activism led to his appointment in 1989, at age 23, as Executive Director of The Fund for Animals; an organization founded by Cleveland Amory.

[citation needed] Pacelle has been associated with 26 successful statewide ballot initiatives to protect animals, including measures to prohibit cockfighting and mourning dove hunting, restrict steel traps and certain poisons, and ban certain farming methods.

[5] Under Pacelle's direction, the HSUS secured the adoption of "cage-free" egg-purchasing policies by several hundred universities and corporations;[7] the phase-out of gestation crates by key pork producers nationwide;[8] the exposure of an international trophy hunting scam;[9] successful congressional votes and litigation to end horse slaughter; and an agreement from the United States Department of Agriculture to begin enforcement of federal laws concerning the transportation of farm animals.

[citation needed] In early 2008, the HSUS's investigation of animal treatment at the Hallmark/Westland Meat Packing Company sparked the largest beef recall in American history and congressional calls for reform of the slaughterhouse inspection system.

[10] In late February 2008, Pacelle testified on the downer cow issue before a subcommittee of the Senate Agriculture Committee on a panel with USDA Secretary Edward Schafer.

[11] Two November 2006 ballot initiatives conducted with HSUS's support outlawed dove hunting in Michigan and abusive farming practices in Arizona.

In January, 2007, several months after passage of the Arizona ballot measure, Smithfield Foods, the largest pork producer in the world, announced that it would phase out the use of gestation crates that immobilize pregnant sows through confinement.

[13] In 2011, Pacelle and Chad Gregory of the United Egg Producers (UEP) agreed to work together in support of federal hen welfare legislation.

These two organizations helped defeat lawmakers in Congress they consider hostile to animals, including Rep. Chris John of Louisiana, Rep. Richard Pombo of California, and Senator Conrad Burns of Montana.

AWA helped oust Rep. Pete Sessions, R-Texas, in the November 2018 election and also Rep. Dana Rohrbacher, D-Calif., whom Pacelle indicated had been hostile to animal welfare issues during their long congressional careers.

[citation needed] The HSUS has faced criticism from various groups during Pacelle's tenure, including the Center for Consumer Freedom, which receives money from the food industry, and Protect the Harvest, which is funded by oilman Forrest Lucas.

[29] The New York Times subsequently reported on an interview with a Humane Society employee who alleges Pacelle sexually assaulted her in his office.

Iowa director Josh Skipworth claimed that it was "ridiculous to put the business outlook over the female employees" in the board's original decision to retain Pacelle as CEO.

One Nebraska rancher and spokesperson for the agriculture councils claimed that Pacelle allowed HSUS to become a "good ol' boys vegan club.

The citation read, "He has played a role in the passage of more than two-dozen federal statutes and 26 successful statewide ballot initiatives, which is why he is a punching bag for puppy mills and pseudo-PR firms that profit from animal cruelty.

[46] The same year, Supermarket News named Pacelle one of its "Power 50", citing his leadership on farm animal welfare issues.